++
Ethyl alcohol is commercially available in the United States
as higher-than-95% concentration, single-dose 1-mL and
5-mL ampules. Alcohol is usually used undiluted in peripheral injections. Injection
of alcohol perineurally is often associated with burning dysesthesias
along the distribution of the nerve. Preceding the injection with
a local anesthetic can abort this significant discomfort, and may
also serve as a test dose for correct placement of the needle.9
++
The neurolytic action of alcohol is by dehydration, extraction
of cholesterol, phospholipids, cerebrosides, and precipitation of
mucoproteins. This action results in sclerosis of the nerve fibers
and the myelin sheath,10 causing demyelination
and subsequent wallerian degeneration. This nonselective process
is observed in peripheral nerve injections, as well as in spinal
nerve roots, after a subarachnoid injection. On histopathologic
examination, patchy areas of demyelination are seen in posterior
columns, Lissauer’s tract, and dorsal roots. Wallerian
degeneration then extends to the dorsal horn.11 Hence,
large-volume injections can result in meningeal inflammatory changes
and degeneration of the spinal cord.
++
Alcohol is hypobaric with respect to cerebrospinal fluid, which
makes it easier to use for subarachnoid neurolysis by the use of
proper positioning of the patient. Concentrations of 50% to 100% have
been typically employed for subarachnoid blocks. The patient is
usually placed in the lateral decubitus position with the painful
site up in order to utilize the hypobaric properties of alcohol.
The patient is then rolled 45 degrees to place the dorsal root at
the contact point of alcohol rise, the so-called lateral-prone position.
A volume of 0.3 mL to 0.7 mL is injected per segment.
++
Absolute alcohol has been used in variable concentrations, with
inconsistent results on sensory and motor differentiation. The lowest
concentration of alcohol used resulting in satisfactory analgesia,
with no paresis or paralysis, is as 33%.12 Concentrations
ranging from 48% to 100% have been associated
with incomplete, temporary, progressive, or persistent motor paralysis.
The general consensus is that, with 95% alcohol, the obliteration
entails the sympathetic, sensory, and motor components of a mixed
somatic nerve.
++
The pharmacologic properties of alcohol have important implications
on clinical use:
++
- Alcohol, unlike phenol and glycerin, is readily soluble
in vivo, resulting in a rapid spread from the injection site. Adequate
neurolysis may require increased volume use, which may result in surrounding
tissue damage.
- In vitro studies have associated alcohol with arterial vasospasm,
which theoretically is the basis for paraplegia after celiac plexus
blocks via spasm of the artery of Adamkiewicz.
- Acetaldehyde syndrome disulfiram-like effect has been described
after neurolysis with alcohol on a patient treated with moxalactam,
a beta-lactam type antibiotic reported to inhibit aldehyde dehydrogenase.13 The
patient experienced flushing, sweating, dizziness, vomiting, and
marked hypotension for 10 minutes after an injection of 15 mL of
67% alcohol for a celiac plexus block. The pain practitioner should
be cautious about patients taking agents with similar properties,
such as metronidazole, chloramphenicol, the beta-lactam-type antibiotics,
the oral hypoglycemic tolbutamide and chlorpropamide, and disulfiram.14
- Neuritis and deafferentation pain, especially with peripheral
and lumbar sympathetic neurolysis, have been associated more commonly
with alcohol than phenol. In the case of lumbar sympathetic neurolysis,
development of genitofemoral neuralgia secondary to the degeneration
of the rami communicants to the L2 nerve root has been well described.15,16 However,
this finding has not been documented in controlled studies.17
- After celiac plexus block with alcohol, serum ethanol levels
ranging between 21 and 54 mg/dL have been reported.18 Even
though these numbers are below the levels to cause the systemic
effects of alcohol intoxication, caution should be used in the setting
of concurrent sedation or use of central nervous system depressants.
++
Phenol is known as carbolic acid, phenic acid, phenylic acid,
phenyl hydroxide, hydroxybenzene, and oxybenzene. It has a benzene
ring with one hydroxyl group substituted for a hydrogen ion. Phenol
is not commercially available in the injectable form, and needs
to be prepared by the hospital pharmacy. At lower concentrations,
phenol has local anesthetic properties, making it more tolerable
than alcohol during injection for neurolysis.
++
Phenol is clear and poorly soluble in water and, in its pure
state, forms a 6.7% solution in water. It is unstable at
room temperature, and when exposed to air, undergoes oxidation turning
reddish in color.19 On the other hand, phenol is
highly soluble in alcohol and other organic compounds. For clinical
use, it is usually mixed with glycerin, from which it diffuses out
very slowly, resulting in limited spread and highly localized tissue
effect. In this form, phenol is viscous at concentrations from 4% to
10%, and hyperbaric compared to cerebrospinal fluid. The
aqueous preparations of phenol also range from 3% to 10% concentrations;
however, this is a more potent neurolytic. Phenol is commonly used
in a contrast-material mixture to facilitate visualization under
fluoroscopy.20
++
Earlier experience had led to the misconception of selective
destruction of small-diameter, unmyelinated nerve fibers21,22—the
C afferents (slow pain); Aδ afferents (fast pain);
and Aλ efferents (muscle tone)—with phenol
neurolysis. Later studies have proven a direct relationship between phenol
concentrations and the extent of nerve destruction.23,24 Nathan
et al have demonstrated the nonselective destruction by phenol showing
histopathologic and electrophysiologic proof of damage to Aα and
Aβ fibers.25
++
At increasing concentrations, phenol causes a range of destructive
changes on the neural tissue. Use of concentrations >5% result
in protein coagulation and nonselective segmental demyelination (i.e.,
wallerian degeneration) similar to alcohol. Concentrations of 5% to
6% generate lysis of nociceptive fibers with minimum adverse
effects. Higher concentrations result in axonal abnormalities, nerve
root damage, spinal cord infarcts, arachnoiditis, and meningitis.
These properties may count for the long-lasting effect of 10% phenol
in sympathetic neurolytic blocks.26,27
++
Phenol in concentrations lower than 5%, when injected
into the subarachnoid space produced mostly sensory blocks, as demonstrated
in a study by Maher and Mehta in 1977. At higher concentrations,
motor block occurred. These properties have made phenol the agent
of choice for epidural neurolysis.28
++
Compared to alcohol, phenol seems to generate shorter duration
and less intense blocks. In one study comparing various concentrations
of alcohol and phenol, Moller et al have equated 5% phenol
with 40% alcohol in neurolytic potency.29 Degeneration
with phenol takes about 14 days, and regeneration is completed in
about 14 weeks.
++
Phenol is rapidly metabolized by liver enzymes via conjugation
and oxidation and excreted by the kidney.30 Inadvertent
intravascular injection or absorption of phenol may cause transient
tinnitus and flushing. Doses higher than the recommended 600- to
2000-mg range can cause convulsions, central nervous system depression,
and cardiovascular collapse. Chronic toxicity may lead to hepatic
and renal insufficiency.31 Although clinical doses
of 1 to 10 mL of 1% to 10% solutions are unlikely
to cause serious toxicity, Boas recommends that phenol should be
avoided for celiac plexus block, because of the proximity to major
blood vessels, and spared for splanchnic nerve block.32 In
an nonrandomized trial of 57 cancer patients receiving peripheral
neurolytic blocks with absolute alcohol or 6% aqueous phenol,
Jain et al reported equal pain relief and a higher incidence of
systemic side effects with phenol.33,34
++
Glycerol, a compound structurally related to alcohol,35 was
discovered accidentally, and quickly found to be clinically useful
in the treatment of intractable facial pain.36–38 In
these studies, percutaneous retrogasserian glycerol rhizotomy for
the treatment of tic douloureux is reported to be far superior to
radiofrequency rhizotomy because no permanent injury to surrounding
tissue is reported. Furthermore, there is preservation of facial
sensation in most patients.39,40 Potential spread
to the subarachnoid space and risk of deafferentation, however,
still remains a risk factor. Especially with the use of pulsed radiofrequency,
well-localized, controlled lesioning still remains a preferred therapy
modality. Long-term follow-up, comparing the two techniques has not
been reported.30
++
Histopathologic examination after intraneuronal glycerol injection
has revealed extensive myelin sheath swelling, axonolysis, and severe
inflammatory response. Electron microscopy confirmed nonselective
wallerian degeneration, phagocytosis, and mast cell degranulation.19
++
The use of ammonium salts was introduced to clinical practice
in 1942 by Bates and Judovich.41 Clinically, the
action of ammonium salts is mainly on C-fiber potentials, with small
effect on A fibers. Clinical information shows that at concentrations
of 10%, ammonium salts preserve motor function with good
analgesia.42 Histopathology reveals acute degenerative
neuropathy when these compounds are injected around a peripheral
nerve, affecting all fibers. Associated adverse effects, such as
nausea, vomiting, headaches, paresthesia, and spinal cord injury,
have resulted in clinical abandonment of ammonia salts in clinical
practice.30
++
Butyl aminobenzoate (Butamben) is an extremely hydrophobic/lipophilic
ester local anesthetic. Investigative work by Shulman and Korsten
is suggestive of a potential role for this compound in the setting
of chronic pain.43,44 Both have used butamben in
suspensions of 2.5% to 10% for epidural, subarachnoid,
and peripheral nerve blocks for malignant and nonmalignant pain
with relative selectivity and prolonged duration.